Role of primary care in opioid prescribing for older head and neck cancer survivors.

BACKGROUND: Older head and neck cancer (HNC) survivors have concerning rates of potentially unsafe opioid prescribing. Identifying the specialties of opioid prescribers for HNC survivors is critical for targeting the settings for opioid safety interventions. This study hypothesized that oncology and surgery providers are primarily responsible for opioid prescriptions in the year after treatment but that primary care providers (PCPs) are increasingly involved in prescribing over time. METHODS: Using linked Surveillance, Epidemiology, and End Results-Medicare data, a retrospective analysis was conducted of adults aged >65 years diagnosed between 2014 and 2017 with stage I-III HNC and who had ≥6 months of treatment-free follow-up through 2019. Starting at treatment completion, opioid fills were assigned to a prescriber specialty: oncology, surgery, primary care, pain management, or other. Prescriber patterns were summarized for each year of follow-up. Multinomial logistic regression models captured the likelihood of opioids being prescribed by each specialty. RESULTS: Among 5135 HNC survivors, 2547 (50%) had ≥1 opioid fill (median, 2.1-year follow-up). PCPs prescribed 47% of all fills (42%-55% each year). PCPs prescribed opioids to 45% of survivors with ≥1 opioid fill, which was a greater share than other specialties. PCPs prescribed longer supplies of opioids (median, 20 days/fill; median, 30 days/year) than oncologists or surgeons. The likelihood of an opioid being prescribed by an oncology provider was four times lower than that of it being prescribed by a PCP. CONCLUSIONS: PCP involvement in opioid prescribing remains high throughout HNC survivorship. Interventions to improve the safety of opioid prescribing should target primary care, as is typical for opioid reduction efforts in the noncancer population.

Radiodensities of skeletal muscle and visceral adipose tissues are prognostic factors in clear cell renal cell carcinoma.

BACKGROUND: Body composition may be related to survival in clear cell renal cell carcinoma (ccRCC) patients but studies have not simultaneously considered adipose and muscle tissue quantity and radiodensity. METHODS: We analyzed data from 1,022 ccRCC patients who underwent nephrectomy between 2000 -2020 at Memorial Sloan Kettering Cancer Center. Skeletal muscle, visceral adipose, and subcutaneous adipose tissue index (SMI, VATI, SATI respectively; cm2/m2) and radiodensity (SMD, VATD, SATD respectively; Hounsfield Units [HU]) were assessed from non-contrast pre-surgical computed tomography scans; clinical and demographic characteristics were available from the time of surgery. Hazard ratios (HR) and confidence intervals (CI) were estimated for overall (OS) and disease-free survival (DFS) through March 2023 in multivariable models that simultaneously accounted for all body composition measures. RESULTS: Median age was 58 years, 69% were male, and 90% White. There were 169 OS events over 8,392 person-years, and 253 DFS events over 7,753 person-years of follow-up. In adjusted analyses, poor OS was associated with lower SMD (-10 HU, HR (95% CI): 1.37 [1.05, 1.77]), and greater VATD (+10 HU: 1.66 [1.06, 2.59]), with similar findings for DFS. Poor survival was also associated with greater VATI (+40 cm2/m2, OS: 1.32 [0.97, 1.79]; DFS: 1.33 [1.04, 1.71]). Associations with SMD were limited to patients with stage 1/2 disease. CONCLUSIONS: Radiodensities of skeletal muscle and visceral adipose tissue may be novel pre-surgical prognostic factors for ccRCC patients. IMPACT: Findings underscore the importance of evaluating the full range of body composition features simultaneously in multivariable models.

Skeletal muscle and visceral adipose radiodensities are pre-surgical, non-invasive markers of aggressive kidney cancer.

INTRODUCTION: Most studies on body composition in kidney cancer have been conducted among patients with metastatic disease. Given that aggressive tumours can adversely impact body composition and even non-metastatic tumours can be aggressive, we evaluated associations between pre-surgical body composition features and tumour pathological features in patients with non-metastatic clear cell renal cell cancer (ccRCC). METHODS: The Resolve Cohort consists of 1239 patients with non-metastatic ccRCC who underwent nephrectomy at Memorial Sloan Kettering Cancer Center between 2000 and 2020. The cross-sectional areas and radiodensities of skeletal muscle, visceral adipose, and subcutaneous adipose tissues were determined from pre-surgical computed tomography (CT) scans at the third lumbar vertebrae using Automatica software. Pearson's correlation coefficients describe inter-relationships among BMI and body composition variables, while odds ratios (OR) and 95% confidence intervals (CI) estimate associations between continuous body composition features (per 1-standard deviation) and advanced stage (Stage III vs. Stages I-II) and high Fuhrman grade (Grades 3-4 vs. 1-2) from multivariable logistic regression models that considered the potential impact of biological sex, contrast enhanced CTs, and early age at onset of ccRCC. RESULTS: The cohort was predominantly male (69%), white (89%), and had a median age of 58. The proportion of patients presenting with advanced stage and high-grade disease were 31% and 51%, respectively. In models that adjusted for demographics and all body composition variables simultaneously, decreasing skeletal muscle radiodensity (i.e., more fat infiltration) but increasing visceral adipose tissue radiodensity (i.e., more lipid depletion) were associated with advanced tumour features. Per 8.4 HU decrease in skeletal muscle radiodensity, the odds of presenting with advanced stage was 1.61 (95% CI: 1.34-1.93). Per 7.22 HU increase in visceral adipose tissue radiodensity, the odds of presenting with advanced stage was 1.45 (95% CI: 1.22-1.74). Skeletal muscle index (i.e., sarcopenia) was not associated with either tumour feature. Similar associations were observed for Fuhrman grade, a more direct marker of tumour aggressiveness. Associations did not differ by sex, contrast use, or age at onset of ccRCC. CONCLUSIONS: Lipid infiltrated skeletal muscle, but lipid depleted visceral adipose tissue were independently associated with advanced tumour features in non-metastatic ccRCC. Findings highlight the importance of evaluating the full range of body composition features simultaneously in multivariable models. Interpreting pre-surgical CTs for body composition for patients may be a novel and non-invasive way to identify patients with aggressive renal tumours, which is clinically relevant as renal biopsies are not routinely performed.

The association between the Mediterranean Diet Score and death from cancer of the head and neck.

PURPOSE: The association between diet quality, captured by the Mediterranean Diet Score (MDS), and mortality was studied among 1184 individuals diagnosed with head and neck cancer (HNC) who reflected on the year preceding diagnosis about their usual diet using National Cancer Institute's Diet History Questionnaire (DHQ). METHODS: Intakes of nine dietary components were scored and summed to construct the MDS (sample: median = 4; range (0-9); lower MDS reflected poorer diet quality; 5-year survival probability = 0.62). Cox regression estimated 5-year hazard ratios (HR) and 95% confidence intervals (95CI) for all-cause mortality and for HNC-specific death for contrasts of MDS quintiles. Effect measure modification (EMM) by tumor features [human papillomavirus (HPV) positivity; anatomic site] and sociodemographic behavioral factors [race, body mass index (BMI), smoking, alcohol consumption] was explored. RESULTS: The 5-year [HR (95CI); P-trend] for all-cause mortality and HNC-specific mortality for highest versus lowest MDS quintile contrasts were [0.51 (0.33, 0.80); 0.014] and [0.43 (0.22, 0.85); 0.004], respectively. A unit increase in MDS adherence resulted in a 15% reduction of the 5-year HR for HNC-specific death for tumors located at the oral cavity [HR (95CI): 0.85 (0.75, 0.96)]. Poor diet quality (MDS ≤ 4) interacted with lower BMI (kg/m2 < 25) and separately with ever-using alcohol to produce 5-year HRs for all-cause and HNC-specific mortality that were statistically significantly larger than the sum of the individual HRs representing each combination (Poor diet quality + lower BMI; Poor diet quality + ever-using alcohol). CONCLUSION: Greater adherence to a Mediterranean diet pattern prior to HNC diagnosis may reduce post-diagnosis mortality.

Body composition and cancer survival: a narrative review.

Interest in understanding the relationship between body composition and cancer survival has remained strong for decades, with a number of recent systematic reviews on the topic. However, the current state of evidence is based on heterogeneous exposure definitions based on anthropometry, yielding inconsistent findings with regard to this association. Recently the field has taken an exciting direction with the application of radiological assessments to measure specific aspects of body composition, yet reconciliation of findings from these modern assessment tools with those from the historic use of anthropometric data proves challenging. In this paper, I briefly review the biological basis for a link between body composition and cancer survival and summarize the epidemiological evidence with consideration to specific exposure measures. As enthusiasm is building around novel assessments, I conclude with a discussion of issues that researchers should be aware of when interpreting results from these new modalities.

Mixture of air pollution, brominated flame retardants, polychlorinated biphenyls, per- and polyfluoroalkyl substances, and organochlorine pesticides in relation to vitamin D concentrations in pregnancy.

Over two-thirds of pregnant women in the U.S. have insufficient 25(OH)D (Vitamin D) concentrations, which can adversely impact fetal health. Several pollutants have been associated with 25(OH)D, but have not been considered in the context of chemical co-exposures. We aimed to determine associations between a broad mixture of prenatal environmental chemical exposures and 25(OH)D concentrations in mid-pregnancy. Stored mid-pregnancy serum samples were assayed from 421 women delivering live births in Southern California in 2000-2003. 25(OH)D, six BFRs, eleven polychlorinated biphenyls (PCBs), six per- and polyfluoroalkyl substances, and two organochlorine pesticides were detected in ≥60% of specimens. Gestational exposures to airborne particulate matter ≤ 10 µm (PM10) and ≤ 2.5 µm (PM2.5), nitrogen monoxide (NO), nitrogen dioxide (NO2), and ozone concentrations were derived from monitoring station data. Bayesian Hierarchical Modeling (BHM) and Bayesian Kernel Machine Regression (BKMR) analyses estimated overall mixture and individual chemical associations accounting for co-exposures and covariates with mean 25(OH)D levels, and BHM was used to estimate associations with insufficient (<75 nMol/L) 25(OH)D levels. Non-mixture associations for each chemical were estimated with linear and logistic models. PM10 [BHM estimate: -0.133 nmol/l 95% Credible Interval (-0.240, -0.026)] was associated with lower 25(OH)D in BHM and BKMR. Higher quantiles of combined exposures were associated with lower 25(OH)D, though with wide credible intervals. In non-mixture models, PM10, PM2.5, NO, and NO2 were associated with lower concentrations, while O3 and PBDE153 were associated with higher 25(OH)D and/or lower insufficiency. While some chemicals were associated with increased and others with decreased 25(OH)D concentrations, the overall mixture was associated with lower concentrations. Mixture analyses differed from non-mixture regressions, highlighting the importance of mixtures approaches for estimating real-world associations.

Hypothetical Interventions on Diet Quality and Lifestyle Factors to Improve Breast Cancer Survival: The Pathways Study.

BACKGROUND: The number of breast cancer survivors is increasing, yet evidence to inform dietary and lifestyle guidelines is limited. METHODS: This analysis included 3,658 participants from the Pathways Study, a prospective cohort of women diagnosed with invasive breast cancer. A healthy plant-based dietary index score (hPDI), an American Cancer Society (ACS) nutrition guidelines score, a 2015 Healthy Eating Index score (HEI), hours per week of moderate to vigorous physical activity (PA), and lifetime cumulative pack-years of cigarette smoking (SM) were each measured at diagnosis, 6, 24, and 72 months. Using g-computation, 5- and 10-year risk ratios (RR), risk differences, and 95% confidence intervals (CI) for all-cause mortality under hypothetical interventions on diet quality, PA, and SM, compared with the natural course (no intervention) were calculated. RESULTS: Hypothetical moderate to extreme interventions on hPDI, ACS, and HEI, each in combination with PA and SM, showed 11% to 56%, 9% to 38%, and 9% to 49% decreases in 5-year risks of all-cause mortality compared with no intervention, respectively [(hPDI: RRmoderate = 0.89, 95% CI: 0.82-0.94; RRextreme = 0.44, 95% CI: 0.26-0.67), (ACS: RRmoderate = 0.91, 95% CI: 0.85-0.96; RRextreme = 0.62, 95% CI: 0.43-0.82), (HEI: RRmoderate = 0.91, 95% CI: 0.84-0.95; RRextreme = 0.51, 95% CI: 0.33-0.72)]. While 10-year relative risks were slightly attenuated, absolute risk reductions were more pronounced. CONCLUSIONS: Interventions to improve diet quality, increase PA, or reduce SM at the time of diagnosis may improve survival among breast cancer survivors. IMPACT: We estimate that over 10% of deaths could be delayed by even moderate adoption of these behaviors.

Associations of Post-Diagnosis Lifestyle with Prognosis in Women with Invasive Breast Cancer.

BACKGROUND: Lifestyle habits can impact breast cancer development, but its impact on breast cancer prognosis remains unclear. We investigated associations of post-diagnosis lifestyle with mortality and recurrence in 1,964 women with invasive breast cancer enrolled in the Kaiser Permanente Northern California Pathways Study shortly after diagnosis with lifestyle information at baseline (2005-2013) and the 2-year follow-up. METHODS: We calculated a post-diagnosis lifestyle score (range, 0-18) based on 9 diet, physical activity, and body weight recommendations from the American Cancer Society/American Society of Clinical Oncology (ACS/ASCO) using follow-up data (body weight also included baseline data); higher scores indicate greater guideline concordance. Similarly, we calculated a pre-diagnosis lifestyle score using baseline data to investigate pre- to post-diagnosis changes. We estimated hazard ratios (HR) and 95% confidence intervals (CI) using Cox proportional hazard models, with follow-up through December 2018 (observing 290 deaths and 176 recurrences). RESULTS: The 2-year post-diagnosis lifestyle score was inversely associated with all-cause mortality (ACM; HR per 2-point increase = 0.90; 95% CI, 0.82-0.98), and breast cancer-related mortality (HR, 0.79; 95% CI, 0.67-0.95), but not recurrence. Relative to women who maintained low concordance with recommendations at both time points, women who maintained high concordance had a lower risk of ACM (HR, 0.61, 95% CI, 0.37-1.03). Improved concordance with some specific recommendations (particularly PA) may be associated with a lower hazard of ACM (HRPA, 0.52; 95% CI, 0.35-0.78). CONCLUSIONS: Results suggest that women with breast cancer may benefit from a post-diagnosis lifestyle aligned with ACS/ASCO guidelines. IMPACT: This information may potentially guide lifestyle recommendations for breast cancer survivors to reduce mortality risk.

Circulating Sex Hormones and Risk of Colorectal Adenomas and Serrated Lesions in Men.

BACKGROUND: Sex hormones have been implicated in the etiology of colorectal neoplasia in women for over 40 years, but there has been very little investigation of the role of these hormones in men. METHODS: Using data from an adenoma chemoprevention trial, we conducted a secondary analysis to examine serum hormone levels [testosterone, androstenedione, DHEA sulfate (DHEAS), and sex hormone binding globulin (SHBG)] and risk of colorectal precursors in 925 men. Multivariable logistic regression models were fit to evaluate adjusted associations between hormone levels and risk of "low-risk" (single tubular adenoma < 1 cm) and "high-risk" lesions (advanced adenoma or sessile serrated adenoma or right-sided serrated polyp or >2 adenomas of any size). RESULTS: Overall, levels of free testosterone, total testosterone, androstenedione, DHEAS, or SHBG were not associated with either "low-risk" or "high-risk" early precursor lesions in the colorectum. CONCLUSIONS: These findings do not support the role of sex hormones in early colorectal neoplasia among men. IMPACT: This large prospective study address a missing gap in knowledge by providing information on the role of sex hormones in colorectal neoplasia in males.

Diet Quality and Breast Cancer Recurrence and Survival: The Pathways Study.

Background: Prior research suggests a relationship between overall diet quality and breast cancer survival, although few studies have reported on this topic. We evaluated whether 4 dietary quality indices consistent with healthy eating recommendations around the time of breast cancer diagnosis were associated with risk of recurrence, cause-specific, and all-cause mortality. Methods: A total of 3660 women diagnosed with invasive breast cancer were included. Diet was assessed an average of 2.3 (range = 0.7-18.7) months after diagnosis, from which 4 dietary quality indices were derived: the American Cancer Society guidelines (ACS), the alternate Mediterranean Diet Index (aMED), the Dietary Approaches to Stop Hypertension (DASH), and the 2015 Healthy Eating Index (HEI). Over 40 888 person-years of follow-up, 461 breast cancer recurrences, and 655 deaths were ascertained. Cox models were used to estimate hazards ratios (HRs) and 95% confidence intervals (CIs). Results: Adjusted comparisons between extreme quintiles showed all 4 dietary quality indices to be inversely associated with all-cause mortality, suggesting a 21%-27% lower risk (ACS HR = 0.73, 95% CI = 0.56 to 0.95; aMED HR = 0.79, 95% CI = 0.61 to 1.03; DASH HR = 0.76, 95% CI = 0.58 to 1.00; HEI HR = 0.77, 95% CI = 0.60 to 1.01). Similar patterns were noted for non-breast cancer mortality (ACS HR = 0.69, 95% CI = 0.48 to 0.98; aMED HR = 0.73, 95% CI = 0.50 to 1.05; DASH HR = 0.55, 95% CI = 0.38 to 0.79; HEI HR = 0.67, 95% CI = 0.48 to 0.94). None of the dietary quality indices were associated with recurrence or breast cancer-specific mortality. Conclusion: Food intake patterns concordant with dietary quality indices consistent with recommendations for healthy eating may be beneficial for women with breast cancer.

Predicting Non-Alcoholic Fatty Liver Disease for Adults Using Practical Clinical Measures: Evidence from the Multi-ethnic Study of Atherosclerosis.

BACKGROUND: Many adults have risk factors for non-alcoholic fatty liver disease (NAFLD). Screening all adults with risk factors for NAFLD using imaging is not feasible. OBJECTIVE: To develop a practical scoring tool for predicting NAFLD using participant demographics, medical history, anthropometrics, and lab values. DESIGN: Cross-sectional. PARTICIPANTS: Data came from 6194 white, African American, Hispanic, and Chinese American participants from the Multi-Ethnic Study of Atherosclerosis cohort, ages 45-85 years. MAIN MEASURES: NAFLD was identified by liver computed tomography (≤ 40 Hounsfield units indicating > 30% hepatic steatosis) and data on 14 predictors was assessed for predicting NAFLD. Random forest variable importance was used to identify the minimum subset of variables required to achieve the highest predictive power. This subset was used to derive (n = 4132) and validate (n = 2063) a logistic regression-based score (NAFLD-MESA Index). A second NAFLD-Clinical Index excluding laboratory predictors was also developed. KEY RESULTS: NAFLD prevalence was 6.2%. The model included eight predictors: age, sex, race/ethnicity, type 2 diabetes, smoking history, body mass index, gamma-glutamyltransferase (GGT), and triglycerides (TG). The NAFLD-Clinical Index model excluded GGT and TG. In the NAFLD-MESA model, the derivation set achieved an AUCNAFLD-MESA = 0.83 (95% CI, 0.81 to 0.86), and the validation set an AUCNAFLD-MESA = 0.80 (0.77 to 0.84). The NAFLD-Clinical Index model was AUCClinical = 0.78 [0.75 to 0.81] in the derivation set and AUCClinical = 0.76 [0.72 to 0.80] in the validation set (pBonferroni-adjusted < 0.01). CONCLUSIONS: The two models are simple but highly predictive tools that can aid clinicians to identify individuals at high NAFLD risk who could benefit from imaging.

Menopausal hormone therapy use and long-term all-cause and cause-specific mortality in the Long Island Breast Cancer Study Project.

Previous studies have observed a reduced mortality risk associated with menopausal hormone therapy (MHT) use among breast cancer survivors. We sought to clarify whether such association could be explained by tumor heterogeneity, specific causes of death, confounding from comorbidities or health behaviors, and a comparison group of women without breast cancer. We interviewed 1508 women newly diagnosed with first primary breast cancer in 1996 to 1997 (~3 months after diagnosis), and 1556 age-matched women without breast cancer, about MHT use history. The National Death Index was used to ascertain vital status after a median of 17.6 years of follow-up (N = 597 deaths for breast cancer subjects). Multivariable-adjusted Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (95%CIs) for all-cause mortality, and cause-specific HR (cHR) for breast cancer and cardiovascular disease (CVD). The Fine-Gray model was used to account for competing causes of death. Among women with breast cancer, ever vs never MHT use was inversely associated with all-cause (HR = 0.77, 95%CI = 0.62-0.95), breast cancer-specific (cHR = 0.69, 95%CI = 0.48-0.98), and CVD-specific mortality (cHR = 0.57, 95%CI = 0.38-0.85). Difference of the association was observed in breast cancer-specific mortality according to hormone receptor status (negative tumors: cHR = 0.44, 95%CI = 0.19-1.01; positive tumors: cHR = 0.96, 95%CI = 0.60-1.53). Among the comparison group, we observed similar, but more modest inverse associations for all-cause and CVD-specific mortality. MHT use was inversely associated with mortality after breast cancer, even after accounting for competing causes of death and multiple confounders, and was evident among women without breast cancer. Potential heterogeneity by hormone receptor status requires more study.

Urinary Estrogen Metabolites and Long-Term Mortality Following Breast Cancer.

BACKGROUND: Estrogen metabolite concentrations of 2-hydroxyestrone (2-OHE1) and 16-hydroxyestrone (16-OHE1) may be associated with breast carcinogenesis. However, no study has investigated their possible impact on mortality after breast cancer. METHODS: This population-based study was initiated in 1996-1997 with spot urine samples obtained shortly after diagnosis (mean = 96 days) from 683 women newly diagnosed with first primary breast cancer and 434 age-matched women without breast cancer. We measured urinary concentrations of 2-OHE1 and 16-OHE1 using an enzyme-linked immunoassay. Vital status was determined via the National Death Index (n = 244 deaths after a median of 17.7 years of follow-up). We used multivariable-adjusted Cox proportional hazards to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the estrogen metabolites-mortality association. We evaluated effect modification using likelihood ratio tests. All statistical tests were two-sided. RESULTS: Urinary concentrations of the 2-OHE1 to 16-OHE1 ratio (>median of 1.8 vs ≤median) were inversely associated with all-cause mortality (HR = 0.74, 95% CI = 0.56 to 0.98) among women with breast cancer. Reduced hazard was also observed for breast cancer mortality (HR = 0.73, 95% CI = 0.45 to 1.17) and cardiovascular diseases mortality (HR = 0.76, 95% CI = 0.47 to 1.23), although the 95% confidence intervals included the null. Similar findings were also observed for women without breast cancer. The association with all-cause mortality was more pronounced among breast cancer participants who began chemotherapy before urine collection (n = 118, HR = 0.42, 95% CI = 0.22 to 0.81) than among those who had not (n = 559, HR = 0.98, 95% CI = 0.72 to 1.34; P interaction = .008). CONCLUSIONS: The urinary 2-OHE1 to 16-OHE1 ratio may be inversely associated with long-term all-cause mortality, which may depend on cancer treatment status at the time of urine collection.

Diabetes and cardiovascular disease mortality among a population-based cohort of women with and without breast cancer.

PURPOSE: We investigated whether the relationship between diabetes and all-cause and CVD-related mortality differed between women with and without breast cancer among a cohort drawn from the same source population. METHODS: We interviewed 1,363 women newly diagnosed with breast cancer in 1996-1997, and 1,358 age-matched women without breast cancer, to assess history of physician-diagnosed diabetes. All-cause (n = 631) and CVD-specific mortality (n = 234) was determined by the National Death Index through 2009. We estimated multivariable-adjusted hazard ratios (HRs) for the rates of all-cause and CVD-specific mortality and, to account for competing causes of death, and subdistribution HRs (sHRs) for risk of CVD-related death. RESULTS: Among women with and without breast cancer, respectively, diabetes was associated with: all-cause mortality [HR (95% CI) 1.52 (1.13, 2.05) and 2.17 (1.46, 3.22)]; CVD-specific deaths [1.74 (1.06, 2.84) and 2.06 (1.11, 3.84)]; and risk of CVD-related death [sHR 1.36 (0.81, 2.27) and 1.79 (0.94, 3.40)]. Differences in effect estimates between women with and without breast cancer did not reach statistical significance (p-interaction > 0.10). CONCLUSION: We found that the positive association between a history of physician-diagnosed diabetes and risk of all-cause and CVD-related mortality is of similar magnitude among a population-based cohort of women with or without breast cancer.

Tobacco Retail Density and Initiation of Alternative Tobacco Product Use Among Teens.

PURPOSE: The rise of noncigarette, alternative tobacco product (ATP) use among adolescents may be due in part to an increase in retail availability of ATPs. We examined whether proximity and density of tobacco retailers near students' homes are associated with a higher likelihood of initiating ATP use over time. METHODS: Using data from 728 adolescents (aged 13-19 years at baseline) residing in 191 different neighborhoods and attending 10 different California high schools, longitudinal multilevel and cross-classified random effect models evaluated individual-level, neighborhood-level, and school-level risk factors for ATP initiation after 1 year. Covariates were obtained from the American Community Survey and the California Department of Education. RESULTS: The sample was predominantly female (63.5%) and was racially and ethnically diverse. Approximately one third of participants (32.5%) reported ever ATP use at baseline, with 106 (14.5%) initiating ATP use within 1 year. The mean number of tobacco retailers per square mile within a tract was 5.66 (standard deviation = 6.3), and the average distance from each participant's residence to the nearest tobacco retailer was .61 miles (standard deviation = .4). Living in neighborhoods with greater tobacco retailer density at baseline was associated with higher odds of ATP initiation (odds ratio = 1.22, 95% confidence interval = 1.07-2.12), controlling for individual and school factors. CONCLUSIONS: Tobacco retailers clustered in students' home neighborhood may be an environmental influence on adolescents' ATP use. Policy efforts to reduce adolescent ATP use should aim to reduce the density of tobacco retailers and limit the proximity of tobacco retailers near adolescents' homes and schools.

Abdominal and gluteofemoral size and risk of liver cancer: The liver cancer pooling project.

Obesity is known to be associated with primary liver cancer (PLC), but the separate effects of excess abdominal and gluteofemoral size are unclear. Thus, we examined the association between waist and hip circumference with risk of PLC overall and by histologic type-hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). The Liver Cancer Pooling Project is a consortium of prospective cohort studies that include data from 1,167,244 individuals (PLC n = 2,208, HCC n = 1,154, ICC n = 335). Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CI) were estimated using proportional hazards regression. Waist circumference, per 5 cm increase, was associated with an 11% increased PLC risk (HR = 1.11, 95%CI: 1.09-1.14), including when adjusted for hip circumference (HR = 1.12, 95%CI: 1.08-1.17) and also when restricted to individuals in a normal body mass index (BMI) range (18.5 to <25 kg/m2 ; HR = 1.14, 95%CI: 1.07-1.21). Hip circumference, per 5 cm increase, was associated with a 9% increased PLC risk (HR = 1.09, 95%CI: 1.06-1.12), but no association remained after adjustment for waist circumference (HR = 0.99, 95%CI: 0.94-1.03). HCC and ICC results were similar. These findings suggest that excess abdominal size is associated with an increased risk of liver cancer, even among individuals considered to have a normal BMI. However, excess gluteofemoral size alone confers no increased risk. Our findings extend prior analyses, which found an association between excess adiposity and risk of liver cancer, by disentangling the separate effects of excess abdominal and gluteofemoral size through utilization of both waist and hip circumference measurements.

A Bayesian Sensitivity Analysis to Partition Body Mass Index Into Components of Body Composition: An Application to Head and Neck Cancer Survival.

Previous studies have suggested a "J-shaped" relationship between body mass index (BMI, calculated as weight (kg)/height (m)2) and survival among head and neck cancer (HNC) patients. However, BMI is a vague measure of body composition. To provide greater resolution, we used Bayesian sensitivity analysis, informed by external data, to model the relationship between predicted fat mass index (FMI, adipose tissue (kg)/height (m)2), lean mass index (LMI, lean tissue (kg)/height (m)2), and survival. We estimated posterior median hazard ratios and 95% credible intervals for the BMI-mortality relationship in a Bayesian framework using data from 1,180 adults in North Carolina with HNC diagnosed between 2002 and 2006. Risk factors were assessed by interview shortly after diagnosis and vital status through 2013 via the National Death Index. The relationship between BMI and all-cause mortality was convex, with a nadir at 28.6, with greater risk observed throughout the normal weight range. The sensitivity analysis indicated that this was consistent with opposing increases in risk with FMI (per unit increase, hazard ratio = 1.04 (1.00, 1.08)) and decreases with LMI (per unit increase, hazard ratio = 0.90 (0.85, 0.95)). Patterns were similar for HNC-specific mortality but associations were stronger. Measures of body composition, rather than BMI, should be considered in relation to mortality risk.

Prediagnosis aspirin use, DNA methylation, and mortality after breast cancer: A population-based study.

BACKGROUND: The authors hypothesized that epigenetic changes may help to clarify the underlying biologic mechanism linking aspirin use to breast cancer prognosis. To the authors' knowledge, this is the first epidemiologic study to examine whether global methylation and/or tumor promoter methylation of breast cancer-related genes interact with aspirin use to impact mortality after breast cancer. METHODS: Prediagnosis aspirin use was assessed through in-person interviews within a population-based cohort of 1508 women diagnosed with a first primary breast cancer in 1996 and 1997. Global methylation in peripheral blood was assessed by long interspersed elements-1 (LINE-1) and the luminometric methylation assay. Promoter methylation of 13 breast cancer-related genes was measured in tumor by methylation-specific polymerase chain reaction and the MethyLight assay. Vital status was determined by the National Death Index through December 31, 2014 (N = 202/476 breast cancer-specific/all-cause deaths identified among 1266 women with any methylation assessment and complete aspirin data). Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs, and the likelihood ratio test was used to evaluate multiplicative interactions. RESULTS: All-cause mortality was elevated among aspirin users who had methylated promotor of BRCA1 (HR, 1.67; 95% CI, 1.26-2.22), but not among those with unmethylated promoter of BRCA1 (HR, 0.99; 95% CI, 0.67-1.45; P for interaction ≤.05). Decreased breast cancer-specific mortality was observed among aspirin users who had unmethylated promotor of BRCA1 and PR and global hypermethylation of LINE-1 (HR, 0.60, 0.78, and 0.63, respectively; P for interaction ≤.05), although the 95% CIs included the null. CONCLUSIONS: The current study suggests that the LINE-1 global methylation and promoter methylation of BRCA1 and PR in tumor may interact with aspirin use to influence mortality after breast cancer.

Adipose Tissue Distribution and Cardiovascular Disease Risk Among Breast Cancer Survivors.

PURPOSE: Cardiovascular disease (CVD) is a major source of morbidity and mortality among breast cancer survivors. Although body mass index (BMI) is associated with CVD risk, adipose tissue distribution may better identify patients with a high risk of CVD after breast cancer. METHODS: Among 2,943 patients with nonmetastatic breast cancer without prior CVD, we used International Classification of Diseases (9th and 10th revisions) codes to identify incidence of nonfatal stroke, myocardial infarction, heart failure, or CVD death. From clinically acquired computed tomography scans obtained near diagnosis, we measured visceral adiposity (centimeters squared), subcutaneous adiposity (centimeters squared), and intramuscular adiposity (fatty infiltration into muscle [Hounsfield Units, scored inversely]). We estimated hazard ratios (HRs) and 95% CIs per SD increase in adiposity accounting for competing risks and adjusting for demographics, smoking, cancer treatment, and pre-existing CVD risk factors. RESULTS: Mean (SD) age was 56 (12) years. Over a median follow-up of 6 years, 328 CVD events occurred. Each SD increase in visceral or intramuscular adiposity was associated with an increase in CVD risk (HR, 1.15 [95% CI, 1.03 to 1.29] and HR, 1.21 [95% CI, 1.06 to 1.37]), respectively). Excess visceral and intramuscular adiposity occurred across all BMI categories. Among normal-weight patients, each SD greater visceral adiposity increased CVD risk by 70% (HR, 1.70 [95% CI, 1.10 to 2.62]). CONCLUSION: Visceral and intramuscular adiposity were associated with increased CVD incidence after breast cancer diagnosis, independent of pre-existing CVD risk factors and cancer treatments. The increased CVD incidence among normal-weight patients with greater visceral adiposity would go undetected with BMI alone. Measures of adipose tissue distribution may help identify high-risk patients and tailor CVD prevention strategies.